Toxic effects of acute and chronic atorvastatin exposure on antioxidant systems, autophagy processes, energy metabolism and life history in Daphnia magna

IF 8.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Chemosphere Pub Date : 2024-12-01 DOI:10.1016/j.chemosphere.2024.143792

Yimeng Wang , Yingshi Hou , Cuiping He , Yufei Zhao , Chunni Duan , Xiangping Nie , Jianjun Li

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Abstract

Atorvastatin (ATV) is a representative for hypolipidemic pharmaceuticals and is widely detectable in aquatic environments around the world. However, there are limited studies on the potential effects of ATV on aquatic non-target organisms, especially on aquatic invertebrates. In the present study, the model organism, Daphnia magna was used to investigate the responses of antioxidant system, autophagy process and energy metabolism under the acute exposure of ATV (24 h–96 h), and the changes of physiological parameters of D. magna in response to chronic ATV exposure (21 d) was addressed as well. The results showed that ATV caused oxidative stress in D. magna and elevated activities of antioxidant enzymes (SOD, GST, GPx, and TrxR) at 48 h. However, the progressively increasing oxidative pressure eventually suppressed antioxidant capacities and triggered the transcriptional autophagy process in organism under the regulation of Sestrin as well as its regulated genes (P62, LC3, ATG1, and ATG4B). ATV also altered the expression of DNA methylation related genes. Unlike the clinical response, we found acute ATV exposure led to lipid accumulation in D. magna, affecting energy metabolism. Chronic exposure of higher concentration of ATV (50, 500 μg L⁻¹) adversely affected growth and reproduction parameters of D. magna, caused delayed molting, reduced body length, and decreased number and delayed time of neonates production. Lethal effects were observed in the 5000 μg L⁻¹ of ATV. The present study investigated the toxic effects and mechanisms of acute and chronic ATV exposure on D. magna to provide a scientific basis for evaluating the potential ecological risks of statins on aquatic invertebrates.

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急性和慢性阿托伐他汀暴露对大型蚤抗氧化系统、自噬过程、能量代谢和生活史的毒性影响

阿托伐他汀（ATV）是降血脂药物的代表，可在世界各地的水生环境中广泛检测到。然而，有关亚托伐他汀对水生非目标生物，尤其是水生无脊椎动物的潜在影响的研究十分有限。本研究以大型蚤为模式生物，探讨了急性接触（24 h-96 h）ATV 对大型蚤抗氧化系统、自噬过程和能量代谢的影响，以及慢性接触（21 d）ATV 对大型蚤生理参数的变化。结果表明，48小时后，ATV会导致大型裸鲤体内氧化应激和抗氧化酶（SOD、GST、GPx和TrxR）活性升高，但逐渐增加的氧化压力最终会抑制抗氧化能力，并在Sestrin及其调控基因（P62、LC3、ATG1和ATG4B）的调控下引发转录自噬过程。ATV 还改变了 DNA 甲基化相关基因的表达。与临床反应不同，我们发现急性接触 ATV 会导致大型蜗牛体内脂质积累，影响能量代谢。长期暴露于较高浓度的 ATV（50、500 μg L-1）会对大型裸鲤的生长和繁殖参数产生不利影响，导致蜕皮延迟、体长缩短、新生儿数量减少和出生时间延迟。在 5000 μg L-1 的 ATV 中观察到了致死效应。本研究探讨了急性和慢性亚甲二氧基乙酸暴露对大型裸鲤的毒性作用及其机制，为评估他汀类药物对水生无脊椎动物的潜在生态风险提供了科学依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemosphere 环境科学-环境科学

CiteScore

15.80

自引率

8.00%

发文量

4975

审稿时长

3.4 months

期刊介绍： Chemosphere, being an international multidisciplinary journal, is dedicated to publishing original communications and review articles on chemicals in the environment. The scope covers a wide range of topics, including the identification, quantification, behavior, fate, toxicology, treatment, and remediation of chemicals in the bio-, hydro-, litho-, and atmosphere, ensuring the broad dissemination of research in this field.